Morphology of tissue damage caused by permanent occlusion of middle cerebral artery in mice

In two series of experimental occlusion of the middle cerebral artery (MCA) in mice, the time course and the evolution of morphological changes were f ollowed. Both series comprised control animals used in experiments for the screening of neuroprotective and therapeutic effects after focal ischemia. In both series the left MCA was permanently occluded and the animals were s acrificed by perfusion fixation at certain time intervals following occlusi on. In the first series the follow up was continued until the 30th day afte r ischemia. In the second, the observation period was extended to two month s. The general question was addressed, whether or not such experimental set tings can contribute to the understanding of cellular (necrosis vs apoptosi s) and tissue (resorption vs scar) reaction. In the two series the technical procedures were only slightly different. Ne vertheless, the development of morphological sequelae was at variance. Diff erences in tissue reaction in both sets revealed features that were rarely observed in previous protocols. In the first series, infarct areas were dif ferent in size, often a central part near the meninges was preserved and ga ve rise to a prominent mesenchymal reaction. In the second series, infarcts had almost constant size and mesenchymal reaction changes were minimal. Th e end product in both series, however, was a shallow groove much smaller th an the primary well demarcated defect. We conclude that minor technical var iations of MCA occlusion in the mouse demonstrate the variability of occlus ion sequelae due to collateral irrigation known from human cerebral patholo gy. On the cellular level, neuronal death is obviously completed during the fir st 24 hours in the infarct core. Thus, the mechanism of neuronal damage can only be best observed by morphology at the transition between completed te rritorial necrosis and unchanged tissue: shrunken neuronal perikarya develo p into pycnotic nuclei, that may be interpreted as apoptosis. A second area of partial damage is marked by gliosis. Astrocytic reaction e xtended far beyond the infarct border, even to the contralateral hemisphere and could represent a component of size compensation.